Under normal conditions, bone tissue manifests a steady-state relationship between the amount of bone matrix synthesized and the amount degraded. In skeletal disease, this steady-state is disrupted resulting either in a marked increase in bone mass (as, for example, in osteopetrosis) or, more commonly, a marked decrement (as, for example, in the osteolytic lesions associated with periodontal disease). In the simplest terms, bone mass is determined by the number, distribution and relative activity of bone-forming (osteoblasts) and bone-resorbing cells (osteoclasts). The work in this laboratory is directed toward identifying and culturing the osteoclast precursor (s), and towards specifying the local and systemic factors involved in regulating precursor recruitment, proliferation and differentiation. To achieve these goals, we are employing a variety of experimental techniques including (1) the use of the chick chorioallantoic membrane as a test site for connective tissue and artificial matrices with osteoclast--inducing potential, (2) the interspecific grafting of bone rudiments and other tissues between embryos of the Japanese Quail and the domestic chicken (to establish, among other things, the source of osteoclast precursors) and (3) the use of modified Boyden chambers to determine what extent chemotaxis plays a role in the recruitment of osteoclast precursors. Our results, to date, indicate that osteoclasts originate from a hematopoietic stem cell; that these precursors are carried to sites of incipient and active bone resorption by the blood vascular system; that progenitor cells are chemotactically attracted by bone-matrix associated proteins and glycoproteins; that osteoclast precursors are induced to differentiate by a factor or factors associated with the mineral phase of bone.